Trial Title:
MUC1 Therapeutic Tumor Vaccine in Advanced Solid Cancers
NCT ID:
NCT05986981
Condition:
Solid Tumor, Adult
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
vaccine
Mucin 1
MUC1
malignant tumor
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
The study flow included a screening period (week -4 to day -1), a treatment period (day 1
to week 8 or 16, including a DLT observation period on days 1-28), an end-of-treatment
visit, and a survival follow-up. The treatment period included the initial treatment
period (day 1 to week 8) and the augmentation period (week 12 to week 16). Subjects after
signing and providing formal informed consent entered the screening period, during which
eight separate administrations of the vaccine were administered, of which the
investigator determined whether to continue treatment from week 8 to week 12 based on a
combination of efficacy, safety, and adherence.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Vaccine
Description:
Dose-escalation trial, according to the classic "3+3" model, divided into three dose
levels of 0.5 mg, 1.0 mg, 2.0 mg for enrollment, is expected to enroll a total of 9-18
subjects (0.5 mg dose group to be enrolled in 3-6 subjects, 1.0 mg dose group is proposed
to be enrolled in 3-6 subjects, 2.0 mg dose group is proposed to be enrolled in 3-6
subjects, and the dose group is proposed to be enrolled in 3-6 subjects, and the dose
group is proposed to be enrolled in 3-6 subjects. dose group is proposed to include 3-6
subjects).
Arm group label:
MUC1 Vaccine
Summary:
This is an investigator-initiated, single-center, open, single-arm, exploratory study of
a therapeutic cancer vaccine for the treatment of advanced solid tumors. A
dose-escalation trial is being conducted in subjects diagnosed with advanced solid tumors
to evaluate the safety and tolerability of the cancer vaccine in subjects with advanced
solid tumors and to preliminarily evaluate the efficacy of the tumor vaccine in subjects
with advanced solid tumors.
Detailed description:
Malignant tumours have become one of the major public health problems that seriously
threaten human health. According to the latest global cancer burden data for 2020
released by the International Agency for Research on Cancer (IARC) of the World Health
Organization (WHO), there will be 19.29 million new cancer cases and 9.96 million deaths
globally in 2020; in 2020, there will be 4.57 million new cancer cases and 3 million
deaths in China, with the number of new cancers in China accounting for 23.7% of the
global incidence and 30% of the global deaths, both of which are the highest in the
world. The number of new cancer cases in China accounts for 23.7% of global incidence and
the number of cancer deaths accounts for 30% of global deaths, both of which rank first
in the world, with lung, liver, stomach, esophagus and colorectal cancers having the
highest mortality rates.
At present, in addition to the traditional surgery, radiotherapy and chemotherapy
treatments for malignant tumours, with the advancement of biological sciences, tumour
immunotherapy has developed significantly, in which antibody drugs and cell therapy
(chimeric antigen receptor T cell, CAR-T) have products on the market. With the deepening
research on the characteristics of tumour cells and the differences in protein
expression, therapeutic cancer vaccines have gradually moved from theory to practice and
have shown good performance in clinical trials.
The therapeutic cancer vaccine YB-01 is a therapeutic cancer vaccine formulation
developed by the Department of Nuclear Medicine of Peking Union Medical College Hospital
and commissioned to be produced by Zhaoyan Biologicals, a company with the qualification
of Good manufacturing practice (GMP), and developed by Yuanben (Zhuhai Hengqin) Biotech
Co. YB-01 cancer vaccine is a recombinant fusion protein with aluminium adjuvant and
CpG182 adjuvant, and its core component is Mucin N-terminal region (MNR), which is
specifically expressed by cancer cells. Mucin1 (MUC1) is a glycoprotein that plays a
pivotal role in tumour formation, growth, invasion, signalling, pro-angiogenesis, anoxia
and chemoresistance. Normal epithelial cells exist with low expression of MUC1, whereas
cancerous cells have high expression of MUC1 (100-fold increase), and this differential
expression is due to the fact that it is abnormally pronounced in biliary pancreatic
carcinoma, cholangiocarcinoma, gastric adenocarcinoma, breast carcinoma and
neuroendocrine pancreatic carcinoma, so that vaccine-induced immune response is only
directed against the cancerous cells, but not against the normal tissues, and
non-glycosylated MUC1 has become an important target for cancer therapy.YB- 01 vaccine
targets MUC1 and enhances humoral and cell-mediated immune responses through immunity to
MUC1 peptide or MUC1 peptide-activated dendritic cells (DC).DC cells activate CD4 T
cells, which promotes the activation of B cells to produce antibodies against MUC1, and
DC cells also activate CD8 T cells, which target and kill tumour cells that express MUC1.
cells expressing MUC1.
Approximately 9-18 subjects will be recruited in this study. The investigational drug
used in the study is the therapeutic cancer vaccine YB-01, and the study is designed to
investigate the safety, tolerability, and preliminary efficacy of the vaccine in subjects
with advanced solid tumours.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. screening period patients are able to understand and voluntarily sign an informed
consent form;
2. males and females between the ages of 18 and 75 years (both ends included);
3. expected survival ≥ 3 months;
4. advanced subjects with histologically or cytologically proven advanced solid tumors
who have failed standard multiline therapy;
5. have at least one measurable lesion (i.e., mass ≥10 mm in diameter and malignant
lymph node ≥15 mm in short diameter on enhanced scan with layer thickness ≤5 mm on
spiral CT) according to the efficacy evaluation criteria for solid tumors, RECIST
version 1.1 (see Appendix 4, Criteria for Evaluating the Efficacy of Solid Tumor
Treatments);
6. Fresh or archived tumor tissue samples within 5 years are available for central
laboratory testing during the screening period (if they are truly unavailable, this
will not affect enrollment);
7. ECOG physical status score of 0 to 2;
8. treatment with other anti-tumor drugs (e.g., chemotherapy, hormone therapy,
immunotherapy, antibody therapy, radiotherapy) prior to the first dose exceeds the 5
half-life of the drug or more than 4 weeks before the first dose (whichever is
shorter);
9. Organ function levels must meet the following requirements (no blood or blood
product transfusion, hematopoietic stimulating factor, albumin, or blood product use
within 14 days prior to the examination): absolute neutrophil count (ANC) ≥ 1.5 ×
109/L, platelet count (PLT) ≥ 75 × 109/L, hemoglobin (Hb) ≥ 90 g/L; serum total
bilirubin (TBIL) ≤ 1.5 Total bilirubin (TBIL) ≤1.5 times the upper limit of normal
value, glutamic transaminase (AST) and alanine aminotransferase (ALT) ≤2.5 times the
upper limit of normal value (if liver metastasis is present, total bilirubin ≤3
times the upper limit of normal value, AST and ALT ≤5 times the upper limit of
normal value are allowed). 10;
10. Pre-menopausal women of childbearing potential must undergo a pregnancy test within
7 days prior to the start of treatment, and the result of the pregnancy test must be
negative and non-lactating; women without childbearing potential may not undergo a
pregnancy test and contraception, provided they are over 50 years of age, have not
used hormone therapy and have stopped menstruating for at least 12 months, or have
been sterilized. All enrolled subjects (either male or female) should use adequate
barrier contraception throughout the treatment period and for 3 months after
completion of treatment.
11. Other toxicity parameters must be NCI-CTCAE v.5.0 Grade 0 or 1.
Exclusion Criteria:
1. Subjects who require long-term systemic application of anti-allergic medications or
who have a history of life-threatening allergic reactions to any vaccine or
medication;
2. those with symptomatic or rapidly progressing central system metastases. Presence of
extensive pulmonary metastases causing respiratory distress; subjects with tumours
in close proximity to or invading large blood vessels or nerves;
3. new cerebrovascular accidents (including ischaemic stroke, haemorrhagic stroke and
transient ischaemic attack) within 6 months prior to screening;
4. acute myocardial infarction, uncontrolled angina pectoris, uncontrolled arrhythmia,
severe heart failure (see Appendix 3, New York Heart Association's Heart Failure
Classification Criteria, NYHA Class ≥ III) and other cardiovascular diseases within
6 months prior to screening;
5. have received immunomodulatory medications within 4 weeks prior to the date of first
vaccination (D1), including, but not limited to, IL-2, CTLA-4 inhibitors, CD40
agonists, CD137 agonists, and IFN-alpha (except for high-risk surgical subjects
using IFN-alpha as an adjuvant therapy if IFN-alpha therapy was discontinued within
the 4 weeks prior to the date of the trial);
6. those with a history of renal insufficiency with serum creatinine levels greater
than 1.5 times the upper limit of normal;
7. have received a blood transfusion, erythropoietin (EPO), granulocyte
colony-stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating
factor (GM-CSF) within 2 weeks prior to the first dose of drug;
8. subjects with skin conditions that may prevent intradermal vaccine from reaching the
target area (e.g., psoriasis);
9. subjects in the Screening Period who continue to have adverse reactions from prior
anti-neoplastic therapy that have not been restored to a CTCAE Version 5.0 grade
rating of ≤ Grade 1 (with the exception of alopecia and platinum-induced
neurotoxicity of ≤ Grade 2);
10. need for concomitant use of steroidal hormonal medications (tumour or non-tumour
related disease); exceptions may be made for those requiring topical (not applied to
the vaccination site) or inhaled steroids;
11. the presence of active or uncontrollable infections requiring systemic therapy
(except for simple urinary tract infections or upper respiratory tract infections)
in the subject within 4 weeks prior to screening; and the presence of antibodies to
the Human Immunodeficiency Virus (HIV), hepatitis B Surface Antigen (SAB) positive
and/or hepatitis B Core Antibody (HBCO) positive with Hepatitis B Virus (HBV)
Deoxyribonucleic Acid (DNA) >1000 copies/mL and Hepatitis C virus (HCV) antibodies
on virological testing during the Screening Period, Subjects who are positive for
antibodies specific to syphilis spirochetes;
12. poorly controlled hypertension (defined as systolic blood pressure ≥160 mmHg and/or
diastolic blood pressure ≥100 mmHg) after treatment;
13. subjects with a history of autoimmune disease [e.g., the following, but not limited
to: interstitial pneumonitis, uveitis, enteritis, hepatitis, pituitary gland
inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism (hypothyroidism
without clinical symptoms or hypothyroidism due to radiotherapy may be included),
subjects with vitiligo or cured asthma that does not currently require any
intervention may be included, subjects requiring bronchodilators for medical
intervention cannot be included];
14. subjects with active ulcers or gastrointestinal bleeding during the Screening
Period;
15. subjects who have received a previous similar therapeutic cancer vaccine or who have
received another vaccine within 4 weeks prior to Screening;
16. subjects with congenital or acquired immunodeficiency;
17. subjects who have participated in other clinical trials within 1 month prior to
screening;
18. subjects with known alcohol or drug addiction;
19. subjects who, in the opinion of the investigator, have an underlying health
condition, mental condition, or social condition that makes the subject unable or
unwilling to comply with the study protocol
20. any other condition which, in the opinion of the Investigator, makes participation
in this study inappropriate.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Peking Union Medical College Hospital
Address:
City:
Beijing
Zip:
100730
Country:
China
Contact:
Last name:
Fang Li, MD
Phone:
+86-010-69154417
Email:
lifang@pumch.cn
Start date:
August 2023
Completion date:
December 2024
Lead sponsor:
Agency:
Peking Union Medical College Hospital
Agency class:
Other
Source:
Peking Union Medical College Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05986981
